Surnames as Markers of Pathologies – Two Statistical Techniques and Their Applications

The objective of this research is to propose and to validate two different statistical techniques to test the hypothesis of an association between surnames and pathologies, in a population participating in a screening procedure for a given pathology. We propose two statistical methods: a first technique is based on the rarefaction method, and second one is based on the principle of resampling, and it can be considered a special case of a randomisation test. Both the techniques are applied to a data set of babies screened for congenital hypothyroidism (CH), and they gave similar results. The large overlapping of the results seems to suggest a substantial validity of the proposed techniques

The mechanical stimulation of myotubes counteracts the effects of tumor-derived factors through the modulation of the activin/follistatin ratio

Activin negatively affects muscle fibers and progenitor cells in aging (sarcopenia) and in chronic diseases characterized by severe muscle wasting (cachexia). High circulating activin levels predict poor survival in cancer patients. However, the relative impact of activin in mediating muscle atrophy and hampered homeostasis is still unknown. To directly assess the involvement of activin, and its physiological inhibitor follistatin, in cancer-induced muscle atrophy, we cultured C2C12 myotubes in the absence or in the presence of a mechanical stretching stimulus and in the absence or presence of C26 tumor-derived factors (CM), so as to mimic the mechanical stimulation of exercise and cancer cachexia, respectively. We found that CM induces activin release by myotubes, further exacerbating the negative effects of tumor-derived factors. In addition, mechanical stimulation is sufficient to counteract the adverse tumor-induced effects on muscle cells, in association with an increased follistatin/activin ratio in the cell culture medium, indicating that myotubes actively release follistatin upon stretching. Recombinant follistatin counteracts tumor effects on myotubes exclusively by rescuing fusion index, suggesting that it is only partially responsible for the stretch-mediated rescue. Therefore, besides activin, other tumor-derived factors may play a significant role in mediating muscle atrophy. In addition to increasing follistatin secretion mechanical stimulation induces additional beneficial responses in myotubes. We propose that in animal models of cancer cachexia and in cancer patients purely mechanical stimuli play an important role in mediating the rescue of the muscle homeostasis reported upon exercise

A geographically distributed bio-hybrid neural network with memristive plasticity

Throughout evolution the brain has mastered the art of processing real-world inputs through networks of interlinked spiking neurons. Synapses have emerged as key elements that, owing to their plasticity, are merging neuron-to-neuron signalling with memory storage and computation. Electronics has made important steps in emulating neurons through neuromorphic circuits and synapses with nanoscale memristors, yet novel applications that interlink them in heterogeneous bio-inspired and bio-hybrid architectures are just beginning to materialise. The use of memristive technologies in brain-inspired architectures for computing or for sensing spiking activity of biological neurons8 are only recent examples, however interlinking brain and electronic neurons through plasticity-driven synaptic elements has remained so far in the realm of the imagination. Here, we demonstrate a bio-hybrid neural network (bNN) where memristors work as "synaptors" between rat neural circuits and VLSI neurons. The two fundamental synaptors, from artificial-to-biological (ABsyn) and from biological-to- artificial (BAsyn), are interconnected over the Internet. The bNN extends across Europe, collapsing spatial boundaries existing in natural brain networks and laying the foundations of a new geographically distributed and evolving architecture: the Internet of Neuro-electronics (IoN).Comment: 16 pages, 10 figure

Telomere length elongation after weight loss intervention in obese adults

INTRODUCTION: Telomeres may be considered markers of biological aging, shorter telomere length is associated with some age-related diseases; in several studies short telomere length has also been associated to obesity in adults and adolescents. However the relationship between telomere complex functions and obesity is still not clear. Aim of the study was to assess telomere length (TL) in adults' obese subjects before and after weight loss obtained by placement of bioenteric intragastric balloon (BIB) for 6months. METHODS: We enrolled 42 obese subjects before and after BIB placement as weight loss intervention. Blood samples were collected in order to obtain DNA from leukocyte to measure TL by quantitative PCR. RESULTS: Data were analyzed only in 37 subjects with complete data; all presented important body weight loss (124.06\ub126.7 vs 105.40\ub123.14, p<0.001) and more interesting they presented a significant increase in TL (3.58\ub10.83 vs 5.61\ub13.29, p<0.001). Moreover we observed a significant positive correlation between TL elongation and weight loss (r=0.44, p=0.007) as well as an inverse correlation between TL at baseline and TL elongation (r=-0.35, p=0.03).The predictors of TL elongation were once again weight loss and short TL at baseline (respectively p=0.007 and p=0.003). CONCLUSIONS: Our study shows that weight loss is associated to telomere lengthening in a positive correlation: the greater weight loss the greater telomere lengthening; moreover telomere lengthening is more significant in those subjects with shortest telomeres at baseline.Introduction: Telomeres may be considered markers of biological aging, shorter telomere length is associated with some age-related diseases; in several studies short telomere length has also been associated to obesity in adults and adolescents. However the relationship between telomere complex functions and obesity is still not clear. Aim of the study was to assess telomere length (TL) in adults' obese subjects before and after weight loss obtained by placement of bioenteric intragastric balloon (BIB) for 6 months. Methods: We enrolled 42 obese subjects before and after BIB placement as weight loss intervention. Blood samples were collected in order to obtain DNA from leukocyte to measure TL by quantitative PCR. Results: Data were analyzed only in 37 subjects with complete data; all presented important body weight loss (124.06 \ub1 26.7 vs 105.40 \ub1 23.14, p < 0.001) and more interesting they presented a significant increase in TL (3.58 \ub1 0.83 vs 5.61 \ub1 3.29, p < 0.001). Moreover we observed a significant positive correlation between TL elongation and weight loss (r = 0.44, p = 0.007) as well as an inverse correlation between TL at baseline and TL elongation (r = - 0.35, p = 0.03).The predictors of TL elongation were once again weight loss and short TL at baseline (respectively p = 0.007 and p = 0.003). Conclusions: Our study shows that weight loss is associated to telomere lengthening in a positive correlation: the greater weight loss the greater telomere lengthening; moreover telomere lengthening is more significant in those subjects with shortest telomeres at baseline

Aberrant Autophagic Response in The Muscle of A Knock-in Mouse Model of Spinal and Bulbar Muscular Atrophy

Spinal and bulbar muscular atrophy (SBMA) is characterized by loss of motoneurons and sensory neurons, accompanied by atrophy of muscle cells. SBMA is due to an androgen receptor containing a polyglutamine tract (ARpolyQ) that misfolds and aggregates, thereby perturbing the protein quality control (PQC) system. Using SBMA AR113Q mice we analyzed proteotoxic stress-induced alterations of HSPB8-mediated PQC machinery promoting clearance of misfolded proteins by autophagy. In muscle of symptomatic AR113Q male mice, we found expression upregulation of Pax-7, myogenin, E2-ubiquitin ligase UBE2Q1 and acetylcholine receptor (AchR), but not of MyoD, and of two E3-ligases (MuRF-1 and Cullin3). TGF beta 1 and PGC-1 alpha were also robustly upregulated. We also found a dramatic perturbation of the autophagic response, with upregulation of most autophagic markers (Beclin-1, ATG10, p62/SQSTM1, LC3) and of the HSPB8-mediated PQC response. Both HSPB8 and its co-chaperone BAG3 were robustly upregulated together with other specific HSPB8 interactors (HSPB2 and HSPB3). Notably, the BAG3: BAG1 ratio increased in muscle suggesting preferential misfolded proteins routing to autophagy rather than to proteasome. Thus, mutant ARpolyQ induces a potent autophagic response in muscle cells. Alteration in HSPB8-based PQC machinery may represent muscle-specific biomarkers useful to assess SBMA progression in mice and patients in response to pharmacological treatments

Multi state survival supervised clustering for radiomics-based cancer subtyping

LAUREA MAGISTRALEContrariamente alla classificazione classica dei tumori che classifica la malattia in base al sito primario di origine, la sottotipizzazione del cancro è un approccio di medicina personalizzata che mira a identificare sottogruppi di individui sulla base di caratteristiche specifiche al fine di somministrare trattamenti su misura per ogni paziente. Un modo per effettuare la sottotipizzazione del cancro è attraverso il clustering di sopravvivenza: un metodo di clustering che tiene conto delle differenze nella sopravvivenza degli individui, oltre alle caratteristiche cliniche. Nel contesto dell’analisi delle immagini mediche, la radiomica è un approccio quantitativo che consente una caratterizzazione non invasiva del tumore estraendo variabili numeriche dalle regioni di interesse segmentate nelle immagini. Durante la fase di diagnosi e monitoraggio di una malattia come il cancro del colon-retto, esami di tomografia vengono eseguite più volte, offrendo la possibilità di estrarre informazioni sull’evoluzione delle variabili osservate misurate in relazione al tempo e alle terapie. In questa tesi, viene proposto il metodo Multi State Survival Supervised Clustering (MS3C) per la sottotipizzazione del cancro. MS3C estende approcci pre-esistenti al fine di eseguire la sottotipizzazione del cancro su un set di dati longitudinali, modellando i dati con un modello multi stato dove le funzioni di intensità di transizione sono modellate con il modello dei rischi proporzionali di Cox. Piuttosto che costruire una matrice di similarità e applicare un algoritmo di clustering non supervisionato, MS3C stima sia la matrice di similarità tramite un processo adattativo che i coefficienti nelle funzioni di intensità di transizione del modello multistato. I rischi stimati nella fase di stima del modello multistato vengono utilizzati come informazioni supervisionate nella fase di stima della matrice di similarità con un algoritmo di ottimizzazione iterativa alternata. L’applicazione di MS3C a un set di dati di pazienti affetti da metastasi epatiche da tumore del colon-retto dimostra la capacità dell’algoritmo proposto di identificare due sotto-gruppi con diverse aspettative di sopravvivenza senza recidiva.Opposed to the classical tumor classification that classifies the disease based on the primary site of origin, cancer subtyping is a personalized medicine approach that aims at identifying subgroups of individuals based on specific characteristics in order to deliver tailor-made treatments to every patient. A way to perform cancer subtyping is by means of survival clustering: a clustering method that takes into account differences in the survival outcome of the individuals in addtion to clinical features. In the context of medical imaging analysis, radiomics are a quantitative approach that allows non-invasive tumour characterization by extracting numerical variables from segmented regions of interest on the images. During the diagnosis and monitoring time of a disease such as colorectal cancer, CT scans are executed multiple times, giving the possibility to extract information about the evolution of the mea sured observed variables in relation with time and treatments. In this thesis, the Multi State Survival Supervised Clustering (MS3C) method for cancer subtyping is proposed. MS3C extends previously existing works in order to perform cancer subtyping on a longitudinal dataset, modelling the data with a Multi State Model where transition intensity functions are Cox Proportional Hazard Model. Instead of building a similarity matrix and running an unsupervised clustering algorithm, MS3C learns the similarity matrix with an adaptive process alongside with the coefficients of the regressors in the transition intesity functions of the Multi State Model. The estimated risks in the learning stage of the MSM are used as supervised information in the similarity matrix learning stage in an alternating iterative optimization algorithm. The application of MS3C to a dataset of patients affected by Colorectal Liver Metastases showcases the ability of the proposed algorithm to identify two subgroups with different disease-free survival expectations

Production of radioisotopes within a plasma focus device

In recent years, research conducted in the US and in Italy has demonstrated production of radioisotopes in plasma focus devices, and particularly, on what could be termed "endogenous" production, to wit, production within the plasma it self, as opposed to irradiation of tar gets. This technique relies on the formation of localized small plasma zones characterized by very high densities and fairly high temperatures. The conditions prevailing in these zones lead to high nuclear reaction rates, as pointed out in previous work by several authors. Further investigation of the cross sections involved has proven necessary to model the phenomena involved. In this paper, the present status of research in this field is re viewed, both with regards to cross section models and to experimental production of radio isotopes. Possible out comes and further development are discussed

A New Technique for Deep in situ Measurements of the Soil Water Retention Behaviour

In situ measurements of soil suction and water content in deep soil layers still represent an experimental challenge. Mostly developed within agriculture-related disciplines, field techniques for the identification of soil retention behaviour have been so far employed in the geotechnical context to monitor shallow landslides and seasonal volume changes beneath shallow foundations, within the most superficial ground strata. In this paper, a novel installation technique is presented, discussed and assessed, which allows extension of the use of commercially available low-cost and low-maintenance instruments to characterise deep soil layers. Multi-depth installations have been successfully carried out using two different sensor types to measure the soil suction and water content up to 7\u2009m from the soil surface. Preliminary laboratory investigations were also shown to provide a reasonable benchmark to the field data. The results of this study offer a convenient starting point to accommodate important geotechnical works such as river and road embankments in the traditional monitoring of unsaturated soil variables

Comunidad de paseriformes nidificantes de la Península Valdés (Patagonia, Argentina)

The Valdes Peninsula is a high-natural value area, located on the east coast of Argentine Patagonia. The aim of the reported research was to analyze the community of breeding passerine birds of the inland areas, with the purpose to identify the species that characterize each community, determining the main environmental typologies frequented, in order to study the relationships between bird richness and abundance, and environmental structure. During the breeding season 2011, 107 point counts were performed. 869 birds belonging to 23 passerine species were contacted and analyzed through a cluster analysis using the Indicator Value method. Results revealed the existence of two different communities: one that essentially refers to the grassy steppe where the characteristic species are Shortbilled Pipit (Anthus furcatus) and Common Miner (Geositta cunicularia), and the other one, which occupies the shrub-steppe consisting of more characteristic species, starting from the Rufous-collared Sparrow (Zonotrichia capensis), the most widespread species. These results update previous results on the community of passerines living in the study area and provide some useful insights for management purposes.La Península de Valdes es un area de gran riqueza natural, localizada en la costa Este de la Pa- tagonia Argentina. El propósito de este trabajo fue analizar la comunidad de aves Passeriformes de las areas internas de la región, con el proposito de identificar las especies que caracterizan cada comuni- dad, determinando las principales tipologias ambientales frecuentadas, para poder estudiar las rela- ciones entre la riqueza y abundancia de aves y la estructura del ambiente. Se realizaron 107 puntos de conteo durante la temporada reproductiva de 2011, en donde se detectaron 869 aves pertenecientes a 23 especies de Passeriformes. Para los análisis se usó el método de agrupamiento por el método del Indicator Value. Los resultados evidencian la existencia de dos diferentes comunidades: una asociada exclusivamente a la estepa herbácea y caracterizada por las especies Cachirla uña corta (Anthus furca- tus) y Minero común (Geositta cunicularia); mientras que la otra, asociada a la estepa arbustiva, es car- acterizada por diferentes especies típicas, como el Chingolo (Zonotrichia capensis), que es la especie de mayor distribución. Estos resultados constituyen una actualización al conocimiento de la fauna de la Península de Valdés, los cuales pueden ser útiles para el manejo y conservación de la avifauna de la región.Fil: Pruscini, Fabio. Università Di Urbino; ItaliaFil: Morelli, Federico. Università Di Urbino; ItaliaFil: Sisti, Davide. Università Di Urbino; ItaliaFil: Perna, Paolo. Universita Degli Di Camerino. Scuola Di Scienze Ambientale; ItaliaFil: Catorci, Andrea. Universita Degli Di Camerino. Scuola Di Scienze Ambientale; ItaliaFil: Bertellotti, Nestor Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Rocchi, Marco Bruno Luigi. Università Di Urbino; ItaliaFil: Santolini, Ricardo. Università Di Urbino; Itali